Transcript Chapter 27. Biomolecules: Lipids

Chapter 27.
Biomolecules: Lipids
Based on McMurry’s Organic Chemistry, 6th
edition
©2003 Ronald Kluger
Department of Chemistry
University of Toronto
About Lipids
 Naturally materials that preferentially extract into
nonpolar organic solvents
 Includes fats, oils, waxes, some vitamins and
hormones, some components of membrane
 General types: esters (“saponifiable”) and those that
can’t be hydrolyzed
Based on McMurry, Organic Chemistry, Chapter
27, 6th edition, (c) 2003
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27.1 Waxes, Fats, and Oils
 Waxes - contain esters formed from long-chain (C16-
C36) carboxylic acids and long-chain alcohols (C24C36)
 Triacontyl hexadecanoate is in beeswax
Based on McMurry, Organic Chemistry, Chapter
27, 6th edition, (c) 2003
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Fats and Oils
 Animal fats and vegetable are triacylglycerols oil
 Triesters of glycerol with three long-chain carboxylic
acids
 Saponification of a fat or oil with (reaction with
aqueous NaOH) yields glycerol and three fatty acids
Based on McMurry, Organic Chemistry, Chapter
27, 6th edition, (c) 2003
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Fatty Acids (from Fats and Oils)
 Straight-chain (C12 - C20) carboxylic acids
 Double bonds are cis-substituted but trans-fatty acid
also occur
 A fat or oil in nature occurs as a mixture of many
different triacylglycerols
 The most abundant saturated fatty acids are palmitic
(C16) and stearic (C18)
Based on McMurry, Organic Chemistry, Chapter
27, 6th edition, (c) 2003
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Unsaturated and Polyunsaturated Fatty
Acids
 Oleic (C18 with one C=C) and linolenic (C18 with 3
C=C) are the most abundant unsaturated
Based on McMurry, Organic Chemistry, Chapter
27, 6th edition, (c) 2003
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27.2 Soap
 A mixture of sodium or potassium salts of long-chain
fatty acids produced by alkaline hydrolysis
(saponification) of animal fat with alkali
Based on McMurry, Organic Chemistry, Chapter
27, 6th edition, (c) 2003
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Cleansing Action of Soap
 The carboxylate end of the long-chain molecule is
ionic and therefore is preferentially dissolved in water
 The hydrocarbon tail is nonpolar and dissolves in
grease and oil
 Soaps enable grease to be dissolved into water
Based on McMurry, Organic Chemistry, Chapter
27, 6th edition, (c) 2003
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Detergents
 “Hard” water contains Mg+2 and Ca+2 that form
insoluble salts with soaps
 Synthetic detergents are alkylbenzene sulfonates that
dissolve dirt like soaps but do not form scums with
Mg+2 and Ca+2 .
Based on McMurry, Organic Chemistry, Chapter
27, 6th edition, (c) 2003
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27.3 Phospholipids
 Phospholipids are diesters of H3PO4, phosphoric acid
 Phosphoric acid can form monoesters, diesters and
triesters
 In general these are known as “phosphates”
Based on McMurry, Organic Chemistry, Chapter
27, 6th edition, (c) 2003
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Phosphoglycerides
 Contain a glycerol backbone linked by ester bonds to
two fatty acids and phosphoric acid
 Fatty acid residues with C12–C20
 The phosphate group at C3 has an ester link to an
amino alcohol
Based on McMurry, Organic Chemistry, Chapter
27, 6th edition, (c) 2003
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Phosphoglyceride Membranes
 Phosphoglycerides comprise the major lipid
component of cell membranes
 Nonpolar tails aggregate in the center of a bilayer
 Ionic head is exposed to solvent
Based on McMurry, Organic Chemistry, Chapter
27, 6th edition, (c) 2003
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Sphingolipids




The other major group of phospholipids
Sphingosine or a dihydroxyamine backbone
Constituents of plant and animal cell membranes
Abundant in brain and nerve tissue, as coating
around nerve fibers.
Based on McMurry, Organic Chemistry, Chapter
27, 6th edition, (c) 2003
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27.4 Prostaglandins
 C20 lipids that contain a five-membered ring with two
long side chains
 Present in small amounts in all body tissues and
fluids
 Many physiological effects
Based on McMurry, Organic Chemistry, Chapter
27, 6th edition, (c) 2003
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Prostaglandin Sources
 Biosynthesized from arachidonic acid (C20
unsaturated fatty acid)
 Catalyzed by cyclooxygenase (COX)
Based on McMurry, Organic Chemistry, Chapter
27, 6th edition, (c) 2003
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27.5 Terpenoids
 Steam distillation of plant extracts produces
“essential oils”
 Chemically related to compounds in turpentine (from
pine sap) called terpenes and thus called terpenoids
 Mostly hydrocarbons (some oxygens) that do not
contain esters (stable to hydrolysis)
Based on McMurry, Organic Chemistry, Chapter
27, 6th edition, (c) 2003
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Terpenoids Are Isoprenoids
 Terpenoid structures are derived from isoprene (2-
methyl-1,3-butadiene) units connected head-to-tail
(Isoprene Rule)
 The term “head-to-tail” means that dissimilar ends
are connected (you can choose which is a “head” and
which is a “tail”)
Based on McMurry, Organic Chemistry, Chapter
27, 6th edition, (c) 2003
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Classification of Terpenoids
 Classified according to the number of di-isoprenoid
(C10) units they contain
 Monoterpenes have 10-carbons, sesquiterpenes
(sesqui = 1 1/2) have 15-carbons from three isoprene
units, and so on
Based on McMurry, Organic Chemistry, Chapter
27, 6th edition, (c) 2003
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Some Important Terpenoids
 The triterpene lanosterol is the precursor of
steroid hormones
 The tetraterpene b-carotene is a source of
vitamin A
Based on McMurry, Organic Chemistry, Chapter
27, 6th edition, (c) 2003
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27.6 Biosynthesis of Terpenoids
 Isopentenyl pyrophosphate (IPP) forms higher
isoprenoids in reactions catalyzed by prenyl
transferase
 Monoterpenoids, diterpenoids, and tetraterpoids arise
from 1-deoxyxylulose 5-phosphate.
Based on McMurry, Organic Chemistry, Chapter
27, 6th edition, (c) 2003
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Mevalonate Pathway to
Isopentenyl Diphosphate
 Begins with the conversion of acetate to acetyl CoA
followed by Claisen condensation to yield acetoacetyl
CoA
 Catalyzed by acetoacetyl-CoA acetyltransferase
Based on McMurry, Organic Chemistry, Chapter
27, 6th edition, (c) 2003
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Aldol Condensation Produces
HMG-CoA
 Carbonyl condensation reaction of acetoacetyl CoA with acetyl
CoA
 Produces 3-hydroxy-3-methylglutaryl CoA (HMG-CoA)
Based on McMurry, Organic Chemistry, Chapter
27, 6th edition, (c) 2003
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Reduction Forms Mevalonate
 HMG CoA is reduced to mevalonate
 Catalyzed by HMG CoA reductase utilizing NADPH
Based on McMurry, Organic Chemistry, Chapter
27, 6th edition, (c) 2003
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Conversion of Mevalonate to IPP
 Pyrophosphorylation gives mevalonyl-PP
 Addition of phosphate from ATP followed by loss of
CO2 and phosphate
Based on McMurry, Organic Chemistry, Chapter
27, 6th edition, (c) 2003
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Conversion of Isopentenyl
Diphosphate to Terpenoids
 For triterpenes and larger, head-to-head coupling of
farnesyl diphosphates gives squalene
Based on McMurry, Organic Chemistry, Chapter
27, 6th edition, (c) 2003
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Mechanism of Isomerization
 Isomerization of IPP to DMAPP is catalyzed by IPP
isomerase through a carbocation pathway
Based on McMurry, Organic Chemistry, Chapter
27, 6th edition, (c) 2003
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Coupling Mechanism
 Nucleophilic substitution reaction in which the double
bond of IPP behaves as a nucleophile in displacing
diphosphate ion leaving group (PPO)
Based on McMurry, Organic Chemistry, Chapter
27, 6th edition, (c) 2003
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Conversions of Monoterpenoids
 Typically involves carbocation intermediates and
multistep reaction pathways catalyzed by a terpene
cyclase
Based on McMurry, Organic Chemistry, Chapter
27, 6th edition, (c) 2003
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27.7 Steroids
 Steroids,are another class of nonsaponifiable lipid,
defined by structure
 Has four fused rings A, B, C, and D, beginning at the
lower left
 Carbon atoms are numbered beginning in the A ring
 The six-membered rings are in fixed chair
conformations
Based on McMurry, Organic Chemistry, Chapter
27, 6th edition, (c) 2003
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Functions of Steroids
 In humans as hormones, steroids are chemical
messengers secreted by glands and carried through
the bloodstream to target tissues
 Also widely distributed as cholesterol
Based on McMurry, Organic Chemistry, Chapter
27, 6th edition, (c) 2003
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Male Sex Hormones
 Testosterone and androsterone are the two most
important male sex hormones, or androgens
 Androstanedione is a precursor
Based on McMurry, Organic Chemistry, Chapter
27, 6th edition, (c) 2003
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Female Sex Hormones
 Estrone and estradiol are the two most important
female sex hormones, or estrogens
 Progesterone is the most important progestin,
steroids that function in pregnancy
Based on McMurry, Organic Chemistry, Chapter
27, 6th edition, (c) 2003
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Adrenocortical Hormones
 Adrenocortical steroids: secreted by the adrenal
glands near the upper end of each kidney
 Mineralocorticoids: control tissue swelling by
regulating cellular salt balance
 Glucocorticoids: regulation of glucose metabolism
and in the control of inflammation
Based on McMurry, Organic Chemistry, Chapter
27, 6th edition, (c) 2003
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Synthetic Steroids
 Made in pharmaceutical laboratories as new drugs
 Includes oral contraceptives and anabolic agents
 Methandrostenolone is an anabolic steroid used for
tissue-building
Based on McMurry, Organic Chemistry, Chapter
27, 6th edition, (c) 2003
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27.8 Stereochemistry of Steroids
 Two cyclohexane rings can be joined in either a cis or
a trans manner
 In cis-decalin, both groups at the ring-junction
positions are on the same side of the two rings
 In trans-decalin, the groups at the ring junctions are
on opposite sides
Based on McMurry, Organic Chemistry, Chapter
27, 6th edition, (c) 2003
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A/B Junction in Steroids
 Steroids can have either a cis or a trans fusion of the
A and B ring
 (B–C and C–D) are usually trans
Based on McMurry, Organic Chemistry, Chapter
27, 6th edition, (c) 2003
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27.9 Steroid Biosynthesis
 Enzyme-catalyzed addition of oxygen atom to
squalene
 Stereospecific formation of an oxirane from an alkene
R
R
O2
Enzyme
O
Squalene
2,3-Oxidosqualene
Based on McMurry, Organic Chemistry, Chapter
27, 6th edition, (c) 2003
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Cyclization to Steroid
 Stork-Eschenmoser mechanism
 Enzyme-catalyzed
 See Figure 27.6
R
O
E-H
HO
Based on McMurry, Organic Chemistry, Chapter
27, 6th edition, (c) 2003
R
protosteryl cation
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